rs2769982

Positions:

• chr20-49908290-A-G
• chr20-49908290-A-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_006038.4(SPATA2):​c.201T>C​(p.Tyr67=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.484 in 1,614,058 control chromosomes in the GnomAD database, including 197,571 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.42 (15643 hom., cov: 33)
  • Exomes 𝑓: 0.49 (181928 hom.)
• Consequence: SPATA2 NM_006038.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.235

Genes affected

SPATA2 (HGNC:14681): (spermatogenesis associated 2) Enables signaling receptor complex adaptor activity and ubiquitin-specific protease binding activity. Involved in several processes, including protein deubiquitination; regulation of necroptotic process; and regulation of tumor necrosis factor-mediated signaling pathway. Located in cytoplasm; fibrillar center; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP7: Synonymous conserved (PhyloP=-0.235 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.765 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPATA2	NM_006038.4	c.201T>C	p.Tyr67=	synonymous_variant	2/3	ENST00000289431.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPATA2	ENST00000289431.10	c.201T>C	p.Tyr67=	synonymous_variant	2/3	1	NM_006038.4	P1
SPATA2	ENST00000422556.1	c.201T>C	p.Tyr67=	synonymous_variant	2/3	2		P1

Frequencies

GnomAD3 genomes AF: 0.422 AC: 64172 AN: 152100 Hom.: 15628 Cov.: 33

Gnomad AFR AF: 0.180

Gnomad AMI AF: 0.343

Gnomad AMR AF: 0.558

Gnomad ASJ AF: 0.381

Gnomad EAS AF: 0.786

Gnomad SAS AF: 0.613

Gnomad FIN AF: 0.599

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.473

Gnomad OTH AF: 0.435

GnomAD3 exomes AF: 0.523 AC: 131543 AN: 251400 Hom.: 36750 AF XY: 0.524 AC XY: 71154 AN XY: 135892

Gnomad AFR exome AF: 0.170

Gnomad AMR exome AF: 0.650

Gnomad ASJ exome AF: 0.364

Gnomad EAS exome AF: 0.782

Gnomad SAS exome AF: 0.609

Gnomad FIN exome AF: 0.595

Gnomad NFE exome AF: 0.471

Gnomad OTH exome AF: 0.514

GnomAD4 exome AF: 0.491 AC: 717206 AN: 1461838 Hom.: 181928 Cov.: 70 AF XY: 0.494 AC XY: 359198 AN XY: 727214

Gnomad4 AFR exome AF: 0.164

Gnomad4 AMR exome AF: 0.636

Gnomad4 ASJ exome AF: 0.374

Gnomad4 EAS exome AF: 0.815

Gnomad4 SAS exome AF: 0.607

Gnomad4 FIN exome AF: 0.596

Gnomad4 NFE exome AF: 0.473

Gnomad4 OTH exome AF: 0.476

GnomAD4 genome AF: 0.422 AC: 64230 AN: 152220 Hom.: 15643 Cov.: 33 AF XY: 0.438 AC XY: 32583 AN XY: 74408

Gnomad4 AFR AF: 0.181

Gnomad4 AMR AF: 0.558

Gnomad4 ASJ AF: 0.381

Gnomad4 EAS AF: 0.786

Gnomad4 SAS AF: 0.614

Gnomad4 FIN AF: 0.599

Gnomad4 NFE AF: 0.473

Gnomad4 OTH AF: 0.438

Alfa AF: 0.443 Hom.: 6700

Bravo AF: 0.404

Asia WGS AF: 0.661 AC: 2296 AN: 3478

EpiCase AF: 0.446

EpiControl AF: 0.445

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.29
DANN	Benign	0.47

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2769982; hg19: chr20-48524827; COSMIC: COSV56868078;